This proposal requests funds to support an international symposium on the biology of chloride entitled: The Enigmatic Chloride Ion: Transport, Regulation, and Roles in Physiology to be held on September 4-8, 2013, at the Marine Biological Laboratory in Woods Hole, MA. This meeting will comprise the Annual Symposium of the Society of General Physiologists (SGP). The annual symposium of the SGP has established its legacy as being the premier and most innovative meeting for physiologists, cell biologists, structural biologists, and biophysicists worldwide that span across all career stages and professional arenas. Recent groundbreaking discoveries demonstrating the pivotal role of chloride in human physiology and disease have led to great insights regarding chloride and its regulation, although this has also opened up a wide array of new questions. With typically d200 participants, SGP symposia are large enough to provide detailed and in depth analyses of a focused area of research, while at the same time being small enough to maximize individual discussions and foster collaborative interactions between students, postdoctoral fellows, new investigators, and established leaders within the field. An ambitious program has been developed for this meeting, enriched both by the list of highly-acclaimed speakers and by the addition of certain features not typical to these symposia. Included in the latter is: (1) a debate on the role of ClC chloride channels in lysosomal acidification to be engaged in by Drs. Thomas Jentsch (Berlin, Germany) and Joseph Mindell (NINDS); (2) a summation by Dr. Criss Hartzell (Emory University), and (3) a reserved last-minute session for presentation of new atomic structures not yet published. The symposium is designed around seven half-day Sessions including: (a) Chicken vs. Egg: Evolutionary relationships between channels and transporters, (b) Models & tools for studying chloride transport in health and disease, (c) Molecular families & regulation, and (d) Atypical anion transporters and channels. In most cases, these are led off with a thematic overview by a leader in that field. The Keynote Address, on the first day, will be given by Dr. Rod MacKinnon (Rockefeller Univ.) on the structural biology of chloride-transport proteins. Of note, the agenda includes a presentation from Dr. Fred VanGoor (Vertex Pharmaceuticals) who has led the successful development of therapeutics against Cystic Fibrosis, a chloride channel disease. These topics represent an integration of physiology and medicine from molecular to human levels with a special emphasis on elevating the pace of discovery by approaches that target chloride transport proteins of relevance to health and disease. We expect that this conference will attract approximately 150-200 basic and translational scientists across all career stages working at the cutting edge of ion channel research. The SGP and the members of the organizing committee are poised to ensure the success of this Symposium. It is our aim that through open dialogue and communication, new and important ideas and novel therapies will emerge as a direct result of this meeting.